Drug Abuse and Dependence

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[edit] Drug Abuse and Dependence

Robert M. Swift

[edit] APPROACH TO THE DRUG-ABUSING PATIENT

Drug abuse and dependence are common problems and therefore are encountered regularly by primary care physicians. The Epidemiological Catchment Area Study, a survey of mental health and substance abuse disorders in nearly 20,000 adult Americans, identified a 7% lifetime prevalence of drug dependence. The high prevalence of drug use is associated with considerable morbidity and mortality. Drugs are strongly associated with violent crime and are responsible for both work-related and non–work-related accidents. Each year, alcoholism is estimated to cause 100,000 excess deaths; illicit drug abuse, 19,000 excess deaths; and tobacco, 400,000 excess deaths. Drug abuse and dependence are major causes of psychologic and social problems including family dysfunction, family violence, and child abuse. The total yearly costs to the U.S. economy from drug abuse and dependence are estimated at $98 billion. Of this, almost $10 billion is attributed to direct health care costs of hospitals, treatment centers, nursing homes, and professional services. Alcoholism and drug dependence are associated with 25% to 50% of all general hospital admissions and 50% to 75% of psychiatric admissions, and contribute to complications and increased costs in those patients admitted to hospitals for other reasons.

Clinical treatment outcome studies have demonstrated that treatment for drug addiction can be effective. However, since drug abuse and dependence are chronic relapsing disorders, treatment for these conditions may not be completely effective or may require multiple treatment episodes. The optimal goal of treatment should be abstinence from drugs. With proper diagnosis, intervention, and treatment, 1-year abstinence rates of 30% to 70% can be achieved. Even patients who are unable to achieve long-term abstinence may still benefit from treatment by having their lives prolonged, their morbidity minimized, and their quality of life improved. Controlled research studies, such as the California Drug and Alcohol Treatment Assessment (CALDATA) Study have demonstrated that addiction treatment is also cost-effective. In this study, approximately seven dollars was saved for every dollar invested in treatment. Reviews of published studies on health care utilization find significant savings in total health care costs when drug abuse treatment is available.

It is therefore important for primary care physicians to properly assess and diagnose substance abuse and dependence, to possess knowledge about therapies for the acute management of intoxicated or withdrawing patients, and to possess knowledge regarding long-term treatment and rehabilitation. An overall biopsychosocial approach to addiction treatment is preferred. A treatment plan that is practical, economical, and based on well-established principles should be utilized. In addition, treatment should be individualized: the patient should be matched to the best modality of treatment for the type and severity of the problems. Substance abuse treatment is complex, since it often involves other family members, legal and forensic systems, public assistance services, schools, and child protection agencies. The ability of the primary care physician to work with professionals from these disciplines is important. This chapter discusses the diagnosis and treatment of drug abuse and dependence in the primary care setting.

[edit] Definitions

Historically, clinical thinking about addictive disorders has been clouded by questions of whether use of addictive psychoactive substances constitutes a medical or a moral problem. The situation is further complicated by ambiguities over the legal status of some drugs. Some governmental authorities consider any use of certain drugs illegal, whereas in other localities, use of the same drugs is permitted for medicinal, recreational, and religious purposes. Thus it may be difficult to ascertain exactly where medically acceptable use ends and problem use begins. An example is marijuana. This substance, illegal in most locations, is now approved for medicinal use in California and Arizona and is also used for religious purposes by at least one religious order.

Language used to describe addictive disorders can be misleading because the words describe other conditions. Commonly used, abuse is a pejorative term that implies voluntary unlawful conduct and does not necessarily connote a disease state, as such. Dependence is a term derived from pharmacology and describes a physiologic state of adaptation that occurs after chronic use of a drug. Tolerance refers to the state in which the physical or behavioral effects of a constant dose of a drug decrease over time, or when a greater amount of the substance is required to produce the same effect. Dependence and tolerance occur with many pharmacologic agents, besides addictive substances. The word addiction is commonly used to describe a repertoire of pathologic behaviors that serve to maintain drug use (e.g., lying, stealing, purchase of illegal drugs).

The American Psychiatric Association (APA) and the World Health Organization (WHO) have declared problem use of psychoactive substances to be medical disorders and have defined these disorders using specific diagnostic criteria. The criteria for Substance-Related Disorders in the Diagnostic and Statistical Manual, Version IV (DSM-IV) of the APA, and the International Classification of Diseases, Version 10 (ICD-10) of the WHO, represent the manifestations of addictive use of alcohol/drugs and include psychologic and social dysfunction, in addition to tolerance and dependence. A special version of the DSM-IV has been adapted for use by primary care physicians. However, the medical definition for substance-use disorders does not rule out the role of personal responsibility for seeking and complying with treatment, and does not excuse patients for crime or damages to others as a consequence of alcohol/substance use.

[edit] Classification of Addictive Disorders

According to the DSM-IV, the acute and chronic effects of psychoactive substances are classified under two major categories: substance-use disorders and substance-induced disorders. The two substance-use disorders are substance-dependence and substance-abuse. Substance-induced disorders include the behavioral and neurologic effects of acute and chronic drug use. These are substance intoxication, substance withdrawal, substance-induced psychotic disorder, substance-induced mood disorder, substance-induced anxiety, substance-induced sleep disorder, substance-induced persisting dementia (and amnestic) disorders, and substance-induced sexual dysfunction. The various disorders are described in Boxes 52-1 and 52-2.

[edit] Substance-Dependence.

Substance-dependence is a maladaptive pattern of substance use with adverse clinical consequences. This includes substance use that is uncontrolled and substance use in spite of adverse consequences. In the DSM-IV nomenclature, abuse is a residual category that describes patterns of drug use that do not meet the criteria for dependence.

[edit] Substance Abuse.

Substance abuse is a residual category that describes patterns of drug use that do not meet the criteria for dependence. Substance abuse is a maladaptive pattern of substance use that causes clinically significant impairment. This may include impairments in social, family or occupational functioning; use in the presence of psychologic or physical problems; or use in hazardous situations, such as driving while intoxicated.

DSM-IV designates 11 distinct classes of psychoactive substances: alcohol; amphetamine or related substances; caffeine; cannabis; cocaine; hallucinogens; inhalants; opioids; nicotine; phencyclidine or related substances; and sedatives, hypnotics, or anxiolytics. Each class is associated with both an organic mental disorder and a substance-use disorder. Under the category of substance-use disorders, 10 classes (all but nicotine) are associated with abuse and dependence; dependence only is defined for nicotine. Polysubstance dependence is defined as using three or more categories of substances. A category for other substance-use disorders includes use of anabolic steroids, nitrate inhalants, anticholinergic agents, and other psychoactive substances.

[edit] Extent of Drug Abuse

The Federal government, researchers, and clinicians utilize national surveys of drug use to determine current incidence and prevalence and to track patterns over time. Each of these survey methods targets different population groups, but the data are generally concordant. Unfortunately, systematic studies of drug abuse prevalence have not been conducted in primary care patient populations; however, the trends are probably similar. Two of the most commonly cited surveys are described below.

The National Household Survey on Drug Abuse is an annual survey of selected households regarding recent, remote, and lifetime drug use. Results of this survey may be biased, since it may miss nontraditional households or those who live on the streets. During 1992, data indicated that approximately 22.9 million persons consumed illicit drugs during the previous year. Marijuana in its various forms was the most commonly used illicit drug, used by 17.4 million persons in 1992. About 7.8 million persons used psychotherapeutic drugs, such as stimulants, sedatives, tranquilizers, and analgesics, for nonmedical reasons. Cocaine in all forms, including crack, was used by almost 5 million persons, and 2 million and 2.4 million persons used inhalants and hallucinogens, respectively. There are estimated to be 1 million regular users of heroin, of whom 15% are in some form of treatment, most commonly methadone maintenance. Trends in substance use are shown in Fig. 52-1.

Figure 52-1 Trends in annual prevalence of an illicit drug use index for eighth, tenth, and twelfth graders. (From Monitoring the future study, University of Michigan.)

The Drug Abuse Warning Network (DAWN) surveys hospitals throughout the United States to obtain reports on drug-related emergency room visits. The data are biased, because the information is based on persons seeking emergency treatment in hospitals. Although it underestimates total use and overrepresents more intensive use leading to acute complications, it provides objective data, rather than data based on self-reports.

Data from these two surveys indicate that casual drug use has declined dramatically since the late 1970s, while intensive use has significantly increased since that time. According to 1993 DAWN data, an estimated 466,900 drug abuse–related emergency room episodes occurred in the United States. This is a 16% increase from the 403,600 episodes found in the 1988 DAWN survey. The rate of drug-related episodes per 100,000 persons age 6 and older increased from 186 in 1988 to 204 in 1993. Of concern is the trend for increased illicit drug and alcohol use—including use of marijuana, cocaine, and inhalants—among the 12 to 17 year olds in the United States. Nearly twice as many adolescents took drugs in the month before being interviewed in 1995 than was the case 2 years before. Heroin use among young adults has also increased, rising from 0.3% among 18 to 25 year olds in 1988 to 1.3% in 1992. Multiple drug use appears to be increasing and is common among opiate, sedative, and stimulant abusers.

[edit] The Causes of Addictive Disorders

Studies of individuals with addictive disorders or at risk for developing substance abuse and dependence have identified many factors that foster the development and continuance of substance use. Genetic, familial, environmental, occupational, socioeconomic, cultural, personality, life stress, psychiatric comorbidity, biologic, social learning, behavioral, and conditioning factors have all been proposed to influence the development of addictive disorders. The relative contributions of any of these factors vary from individual to individual and no single factor accounts for all of the risk.

The influence of genetic factors in addictive disorders has been primarily studied in alcohol dependence; less is known about genetic influences in drug dependence. However, a recent study of 1934 female twins found higher concordance rates for abuse and dependence of cocaine and marijuana in identical twins than fraternal twins, suggesting that genetic factors are important. Similar results were found in a study of male twin pairs. The identification of specific genes that predispose one to drug abuse is an active area of investigation.

Advances in neurobiology have led to an increased understanding of the neurochemistry of drug and alcohol dependence. It is hypothesized that the pleasurable, stimulating, and positively reinforcing effects of alcohol and other drugs of abuse are mediated by a brain dopaminergic pathway that projects from the ventral tegmental area to the nucleus accumbens. Repeated drug use sensitizes the system and leads to the development of dependence.

[edit] ASSESSMENT AND DIAGNOSIS

[edit] History

All patients should be screened for alcohol, drug, and tobacco use as part of the routine medical history and examination. Although some patients present with drug use as a chief complaint, others present with medical or surgical problems and only later reveal a substance-use disorder through physical or laboratory findings or incidental discovery. Often, patients may be reluctant to report the extent of their drug use out of shame or fear of social or legal consequences. Inherent in addictive illness is resistance by the addict and significant others to consider that drugs are a problem. This minimization and rationalization of the problem is usually referred to as denial; denial permits the continued propagation of the addiction.

The best way to elicit accurate information is through a supportive, therapeutic relationship. In the context of this relationship, the physician should conduct a detailed drug and alcohol history, conduct a physical and mental status examination, order and interpret necessary laboratory tests, and meet with family or significant others to obtain additional information. If the presence of drug use is not recognized, the addictive disease will continue unabated.

To obtain information about the patient's drug and alcohol use, many physicians routinely ask quantity and frequency questions about psychoactive substances, such as "How much?" and "How often?" These types of questions are most useful in low to moderate drug users. Heavy users tend to underreport their use and quantity, and frequency questions can be unreliable in this group. It is more effective to explore whether the heavy user has experienced deleterious social or behavioral consequences from drug use, or has poor control of use.

Several formalized interviews have been developed that discriminate alcoholism using these criteria. The CAGE questionnaire is a simple four-item test that uses the letters C, A, G, and E as a mnemonic for questions about alcohol use (Box 52-3). A positive answer on more than two questions is considered suspicious for alcohol abuse. The CAGE may be a better predictor of alcoholism in medical patients than laboratory tests. The CAGE is often adapted to drug use, as well.

Two interviews that effectively address the behavioral consequences of drug abuse are the Drug Abuse Screening Test (DAST) and the Addiction Severity Index (ASI). These instruments have been primarily utilized in clinical research and have not been widely used in clinical practice.

Other items in the medical history that should increase suspicion about substance use include divorce, problems at work (job loss, tardiness, absenteeism, work-related injuries), injuries (falls, auto accidents, fights), arrests, driving while intoxicated, leisure activities involving drugs or alcohol, and financial problems. Having a drug-or alcohol-abusing parent or spouse increases the risk for substance use.

[edit] Other Drugs and Medications.

The propensity to freely exchange one drug for another, or to use them simultaneously, is common. Studies indicate that a high percentage of problem drug users, particularly those under the age of 30, use at least one other drug regularly, including nicotine. Some 50% to 75% of heroin addicts, 80% of cocaine addicts, and 40% of cannabis addicts are addicted to alcohol. Over 80% of drug users are also nicotine-dependent. In obtaining a history of drug use and related consequences, a careful screen for alcohol, tobacco, and other drugs is mandatory.

[edit] Physical Examination

During the routine physical examination, the examining physician needs to be alert for findings indicative of drug abuse or dependence. A physical examination can provide important information about the presence of substance use and its medical complications. Physical stigmata of substance use can be due to the drug used or can be associated with the route of administration. Route-specific problems include the presence of a necrotic nasal septum from cocaine nasal insufflation, as well as respiratory and oropharyngeal problems in smokers of cocaine, cannabis, heroin, or nicotine; intravenous drug users may show track marks of intravenous injection and signs and symptoms of human immunodeficiency virus (HIV)-related illnesses and hepatitis B or C regardless of the drug injected. Medical consequences specific to each organ system are discussed below.

[edit] Constitutional Symptoms.

Heavy users of any drug may show general physical debilitation, including weight loss and malnutrition, or evidence of repeated trauma, especially to the head. Fatigue, fevers, night sweats, and chills of unknown significance occur commonly in intravenous drug users; however, such symptoms can be signs of more serious systemic infections, including endocarditis, tuberculosis, and HIV.

[edit] Skin.

The examination of the skin can provide evidence of intravenous drug use and its duration. The examination must be complete and include skin on unexposed areas. Fresh abscesses, cellulitis, and tissue necrosis are all signs of recent drug use. Injection trauma is usually more common with cocaine, resulting from tissue vasoconstriction produced by the drug; however, this can occur with any drug. Parallel needle marks, a single row of scars, hyperpigmentation overlying a vein, and palpably sclerotic veins are all signs of chronic intravenous use. In those patients with absent peripheral veins, the axillary, penile, internal jugular, and femoral veins should be observed for signs of injection. Such patients are at risk for venous and lymphatic insufficiency, leading to lymphedema and systemic infection. Trauma to the skin, including abrasions, lacerations, and cigarette burns, is often observed in drug users. Excoriations can result from opiate-induced pruritus, poor hygiene, or cocaine-induced tactile hallucinations. Although Kaposi's sarcoma is uncommon in heterosexual drug abusers with acquired immunodeficiency syndrome (AIDS), other skin infections including herpes zoster are observed.

[edit] Head and Neck.

Perforation of the nasal septum is often found in nasal drug users, particularly those using stimulants. Poor dentition is extremely common among opiate and stimulant users. Jaundice and scleral icterus usually indicate the presence of acute hepatitis of viral or toxic etiology. Ophthalmoscopic examination of the retina may disclose emboli, ischemia, and central nervous system (CNS) disease associated with AIDS. Infections of the mucous membranes, especially oral candidiasis, are also common in AIDS patients.

[edit] Chest.

Drug users of all types may develop cardiac disease. Cocaine and other sympathomimetic stimulants can induce tachycardia, dysrhythmias, and myocardial ischemia. Congestive heart failure involving the right or left ventricles can have multiple etiologies, including pulmonary disease from injection emboli, and heart valve disease from infection, infarction, or cardiomyopathy. Cardiomyopathy is associated with heroin, cocaine, alcohol, and organic solvent use.

Pulmonary disease is common in drug users. Most drug users are also heavy tobacco users. Smokers of marijuana, cocaine, or other drugs are at greater risk for the development of lung disease, including pneumonias. Opiate and sedative abusers are at particular risk because of suppression of their respiration and cough reflexes, and HIV-positive patients because of immune impairment. In HIV-positive patients, the possibility of tuberculosis, atypical mycobacterium infection, or Pneumocystis carinii or other opportunistic infection should be considered on the development of dyspnea and cough.

Male users of marijuana or methadone may present with drug-induced gynecomastia. Chronic alcohol use or other liver disease should also be considered in such patients.

[edit] Abdomen.

Hepatitis is common in drug users and a complete examination of the liver should be performed to assess tenderness to palpation and hepatomegaly. Splenomegaly is a relatively common finding in otherwise healthy parenteral drug users. Enlargement of the spleen should, however, prompt closer examination of the lymph nodes to rule out other systemic diseases including HIV.

Prostitution is common in both male and female users of illicit drugs. Genital/pelvic and rectal examinations should be conducted to exclude venereal disease and cervical cancer. Blood in the stool may be due to anal sex, chronic constipation from opiates, and gastritis due to alcohol or consumption of drugs containing aspirin.

[edit] Lymphatic System.

Adenopathy is common in injection drug users; its presence, particularly in the groin and axillae, is likely related to repeated injection of antigenic and infectious materials into the extremities. However, adenopathy may indicate more serious illness such as systemic infections and lymphomas. Lymphedema of the extremities due to chronic venous obstruction is commonly observed in injection drug users.

[edit] Nervous System.

Peripheral neuropathies are commonly observed in alcohol and drug users. Brachial plexus neuropathy (so-called "Saturday night palsy") is seen with drugs producing obtundation, including opiates, alcohol, and sedatives. Peripheral neuropathies can occur secondary to tissue necrosis from drug injection, associated infections, or inflammatory response. CNS conditions are also common. Cerebral infarction or bleeding due to stimulants and cocaine may produce a variety of focal neurologic findings. Chronic solvent use can induce cerebellar ataxia and cerebral atrophy. HIV-positive patients are subject to bacterial, viral, and fungal infections of the CNS.

[edit] Mental Status Examination

All patients should receive a screening mental status examination to assess cognitive and psychiatric function. Psychiatric disorders such as mood disorders, anxiety disorders, attention deficit disorder, and personality disorders frequently coexist with substance use disorders. Drug use is also associated with head trauma. The screening mental status examination should at minimum include an assessment of orientation (person, place, and time), memory (recent and remote), and speech and thought processes. Slurred speech or speech that is not normal in form or content suggests drug intoxication or the presence of other mental disorders. If abnormalities are found on the mental status examination, a more extensive psychologic and psychiatric assessment should be conducted to formally assess attention, cognition, and mood.

[edit] Laboratory and Toxicologic Screening for Substance Use

As part of the physical assessment, patients should receive routine laboratory testing, including complete blood count, tests of kidney and liver function, and a urinalysis. If intravenous drug use is suspected, serologic testing for hepatitis B and C and HIV should be considered. All patients tested for viral hepatitides and HIV, regardless of whether the results are positive or negative, should receive both pretest and posttest counseling about the meaning of the results and about the dangers of needle sharing and unprotected sex. Patients with positive hepatitis C serology should be referred for follow-up liver function tests, viral load, possible liver biopsy, and treatment with interferon-α or other antiviral agents. Patients with positive HIV serology should be referred for T lymphocyte subset testing and antiretroviral therapy.

Serum and urine toxicologic screens have an important role in the assessment and treatment of patients with substance-use disorders. However, it is important that physicians be aware of how to properly conduct such testing and how to interpret the results. Optimally, informed consent should be obtained for all drug testing unless the patient is unable to give consent or testing is required by law. Most toxicologic analyses are conducted on urine, although analyses are sometimes conducted on blood, amniotic fluid, saliva, and hair. To minimize errors and adulteration of the sample, all samples should be obtained while the patient is directly observed. Positive test results should be confirmed with a second test using a different analytic method, since compounds in foods or medications that are chemically similar to drugs can yield false-positive results under certain analytic methods. A positive test suggests use of a psychoactive substance, but it may not indicate the extent of use, when it occurred, or whether there was behavioral impairment.

[edit] TREATMENT

[edit] Overview

The most effective way to reduce the medical, social, and psychologic impact of drugs is through effective treatment. Addiction treatment may be defined as medical, psychologic, and social interventions to reduce or eliminate the harmful effects of drugs on the individual, his or her family and associates, and others in society. Although abstinence is the goal of most treatments, reductions in quantity and frequency of drug use can still bring about "harm reduction." Treatment usually consists of the following components:

• Intervention: initiation of treatment and/or referral
  
• Detoxification: removal of drug from the body and the treatment of withdrawal
  
• Rehabilitation: medical, psychologic, and social measures to help avoid the use of psychoactive substances in the future
  
• Aftercare: processes to assist in maintaining a drug-free state
  

Treatment for substance abuse and dependence ranges from very low cost, less intensive methods (e.g., brief advice to stop drug use, information on self-help programs) to higher cost, more intensive methods (e.g., inpatient detoxification, residential rehabilitation programs). There are also many different orientations toward treatment, ranging from the medical/biologic to the spiritual/religious, and from total abstinence to substitution therapies (such as methadone maintenance), which are utilized to different extents by different programs.

At any given time, a large number of individuals are undergoing treatment for drug and alcohol problems. One government survey of treatment programs found more than 800,000 clients are in active alcohol or drug treatment in specialized treatment programs on any given day: 29% are in treatment for drug addiction, 45% for alcoholism, and 26% for combined drug addiction and alcoholism. However, studies indicate that a far greater number of individuals require intervention and treatment.

For patients with substance dependence, the goals of treatment usually include the establishment of a drug-free state. If total abstinence is not obtainable, a significant reduction in harmful drug or alcohol use will still be of some benefit. For patients with substance abuse, the goal should be a reduction in harmful drug or alcohol use. All physicians should be able to assist patients who are identified as having potential drug disorders by using a number of treatment strategies that include brief interventions, counseling, pharmacotherapy, and referral to specialized treatment and other community programs.

For all patients, treatment goals should include psychologic, medical, family, and social interventions to reduce or eliminate the harmful effects of drugs. Changes in living situation, work situation, or friendships may be necessary to decrease drug availability and to reduce social pressure to use drugs. Individual and group psychotherapy is necessary for understanding the role of the drug in the individual's life, improving self-esteem, and relieving psychologic distress. The treatment of underlying psychiatric illness and pain is important, since this may reduce the need for self-medication. Although most treatment can be provided in an outpatient setting, halfway houses, therapeutic communities, and other residential treatment situations may be necessary to ensure a drug-free environment. Self-help groups, such as Narcotics Anonymous (NA), Cocaine Anonymous (CA), Alcoholics Anonymous (AA), ALANON, and Rational Recovery, provide effective treatment, education, emotional support, and hope to patients and their families.

When a patient is referred to a specialized addiction treatment program or an addiction treatment professional, it is important for the primary care physician to remain in contact with the patient, the family, and the other clinicians, so as to maintain continuity of care and to help coordinate treatment.

[edit] Legal Aspects of Addiction Treatment

State and federal laws can influence drug treatment in several ways. First, the possession and use of many drugs or drug paraphernalia are often criminal offenses. Persons arrested for drug use or possession may be remanded to involuntary treatment for a specified duration by criminal courts or drug courts. Such patients may enter treatment to avoid incarceration or to maintain a driver's license or other professional license. Because these patients do not voluntarily choose to enter treatment, they may see treatment as a punishment and present resistance to treatment. Indeed, the physician may be placed in the position of having to inform the court or other authorities should the patient leave treatment or relapse to drug use. Optimally, treatment should proceed according to a written plan, so that each party understands his or her respective responsibilities and options and so that misunderstandings do not occur later. Physicians should educate themselves about federal and state confidentiality laws pertaining to substance abuse treatment, as well as institutional policies on confidentiality and patient rights.

Law or rules of regulatory agencies may determine the format of certain treatments. Methadone maintenance is an example of such a treatment. The guidelines for methadone maintenance were instituted by an act of Congress that established treatment eligibility, methadone dosages that may be used, the frequency of service delivery, and the ancillary psychologic, social, and medical services that must be provided for patients. The Food and Drug Administration (FDA) and the Drug Enforcement Administration (DEA) tightly regulate methadone maintenance treatment.

[edit] Intervention

After identification of drug abuse or dependence, the physician needs to provide feedback on diagnosis and treatment options and to assess the individual's readiness to engage in treatment. Surveys of physicians demonstrate a lack of confidence in treating substance abuse and dependence. However, in the past decade, several methods have been developed to help primary care physicians successfully intervene with patients. The Physician's Guide to Helping Patients With Alcohol Problems, recently released by the National Institute on Alcohol Abuse and Alcoholism (NIAAA), presents useful intervention methods.

A model of human behavior that has been widely accepted to explain the process of behavioral change in addictive behaviors is the transtheoretic model of behavioral change. The transtheoretic model posits that behavioral change is a series of stages: the precontemplative stage (not even thinking about changing); the contemplative stage (thinking about changing); the action stage (making efforts toward change); and the maintenance stage (maintaining the changes). Understanding the stage that the patient is in at the time of intervention can assist with optimizing the intervention. For example, a patient in the precontemplative stage would benefit most from basic education about his or her disorder and its consequences; a patient in the action phase would benefit most from receiving skills to help with avoiding addictive substances. The goal of the intervention is to move the patient from precontemplation into contemplation or from contemplation into action (treatment).

Brief interventions conducted in a supportive manner have proven extremely effective in enhancing entrance into alcoholism treatment. Brief interventions can consist of one or more sessions in the physician's office, during which education about substance use and dependence is provided and a plan for cutting down or eliminating substance use is negotiated. The patient and physician together should develop a contract, preferably written, defining the treatment and intervention plan. A formal means of assessment of effectiveness and follow-up should be part of the plan. Motivational interviewing, a technique that identifies and motivates the patient to utilize his or her own treatment resources, has been shown to be effective in engaging patients in treatment and reducing use of addictive substances.

Unfortunately, drug users are frequently uninterested in substance abuse treatment or medical treatment for associated problems. The denial of problems or the rejection of necessary medical treatment on the part of the patient can produce frustration, anger, and discouragement in the clinical personnel who are attempting to help the patient. The physician needs to keep a clinical and nonjudgmental perspective, and to recognize that rejection of treatment is part of the behavior associated with addiction.

[edit] Detoxification and Treatment of Withdrawal

Many patients entering treatment require detoxification to achieve a drug-free state and to minimize morbidity associated with withdrawal. Ideally, detoxification should be closely supervised. This may be accomplished in an outpatient, inpatient, or residential setting depending on the drug used, the level of dependence, and the presence of coexisting medical and psychiatric problems. Several methods for drug detoxification are described in Box 52-4.

[edit] Withdrawal.

Withdrawal is a distinct physiologic and behavioral state that follows cessation or reduction in the amount of drug used. In general, the signs and symptoms of withdrawal are the opposite of those that the drug produces (e.g., withdrawal from depressants produces excitation). The proposed neurobiologic mechanism for withdrawal is a change in the number of postsynaptic neurotransmitter receptors or in receptor sensitivity that occurs with chronic drug use. It should be emphasized that withdrawal is not specific to addictive substances, chronic use of medications such as β-adrenergic blockers, antihistamines, antidysrhythmics, and antidepressants may be associated with a withdrawal syndrome following drug discontinuation.

[edit] SPECIFIC DRUGS

The following section describes the pharmacology and treatment of drug intoxication and dependence induced by specific drugs.

[edit] Sedatives and Hypnotics

[edit] Intoxication.

Sedatives and hypnotic drugs (e.g., benzodiazepines, barbiturates), sometimes referred to as downers or minor tranquilizers, consist of drugs that have depressant effects on the CNS. This class of drugs includes barbiturates, benzodiazepines, ethchlorvynol, glutethimide, meprobamate, and γ-hydroxybutyrate. Sedative medications are a major source of drug emergencies including overdose. Yet, they are among the most prescribed drugs, and are routinely used for their anxiolytic and hypnotic effects. Patients may obtain these medications illicitly from the street or from physicians who unwittingly (or purposely) may be contributing to abuse or dependence. Most of the medications in this group augment the activity of the inhibitory brain neurotransmitter, γ-aminobutyric acid (GABA). Specific binding sites at the chloride channel–GABA receptor complex in neurons exist for benzodiazepines, barbiturates, and other drugs. When these sites are occupied by drug, increased chloride conductance leads to hyperpolarization and inhibition of neurons.

Manifestations of intoxication from sedatives and tranquilizers include initial euphoria, followed by sedation, slowed mention and coordination, confusion, and loss of consciousness. At higher doses, depressants can cause hypotension, bradycardia, and slowed respiratory rate and coma. Impaired respiration can lead to acidosis, dysrhythmias, arrest, and death. Many sedative overdoses involve multiple medications, including psychotropic medications (antidepressants, antipsychotics) and alcohol that can potentiate respiratory and CNS suppression. The length of sedative intoxication depends on the medication dose, the medication half-life, and whether use is acute or chronic. Chronic users show increased tolerance and more rapid metabolism.

The treatment of sedative intoxication is generally supportive. For patients presenting within an hour of intoxication, induction of vomiting or gastric lavage followed by activated charcoal administration may prevent absorption of pill fragments remaining in the stomach. Obtunded patients require close monitoring and respiratory support if respiratory distress is noted. Alert patients need monitoring and protection from harm.

[edit] Sedative Withdrawal.

Chronic sedative use leads to tolerance, physical dependence, and withdrawal when medication is stopped or the dose is reduced. Signs of withdrawal are agitation; increased psychomotor activity; tremulousness; fever; sweating; delirium; convulsions; tachycardia; hypertension; coarse tremor of tongue, eyelids, and hands; and seizures. Symptoms of withdrawal are anxiety, euphoria, depression, incoherent thoughts, hostility, grandiosity, disorientation, and tactile, auditory, and visual hallucinations. Typically, the period of withdrawal depends on the half-life of the medication. For short-acting medications such as triazolam, withdrawal can begin within hours of stopping the medication and may persist for 2 to 3 days. For intermediate-acting sedatives (e.g., pentobarbital, alprazolam) the peak of withdrawal is 2 to 4 days, and the typical duration of withdrawal is 4 to 7 days; for long-acting sedatives (e.g., diazepam, phenobarbital) peak period of withdrawal is 4 to 7 days, and duration 7 to 14 days.

[edit] Treatment.

Sedative-dependence treatment occurs in two stages, detoxification and long-term rehabilitation. Detoxification can be accomplished by gradually tapering the drug, substituting another depressant drug that shares pharmacologic cross-tolerance, or administering another agent to suppress withdrawal symptoms. Benzodiazepines show cross-tolerance with each other and with most other sedative/hypnotic drugs and alcohol. Therefore benzodiazepines can be substituted for other benzodiazepines and barbiturates and vice versa. The conversion for equivalent doses can be calculated if doses are actually known prior to taper. A long half-life medication is usually more effective than short-acting preparations in suppressing withdrawal symptoms, in producing a gradual and smooth transition to the abstinent state, and in enhancing patient compliance.

The duration of the tapering schedule is determined by the half-life of the sedative drug that is being withdrawn. (1) For intermediate-acting sedatives such as alprazolam or pentobarbital, 7 to 10 days of a gradual taper with a long-acting benzodiazepine or barbiturate is often sufficient: 7 days for low-dose and short duration of use and 10 days for high-dose and long duration of benzodiazepine use. In the case of alprazolam, because of higher rates of withdrawal seizures, the use of phenobarbital substitution is recommended for the taper. (2) For the long-acting benzodiazepines, 10 to 14 days of a gradual taper with a long-acting benzodiazepine or barbiturate is often sufficient: 10 days for low-dose and short duration and 14 days for high-dose and long duration of use. The doses can be given in qid or tid intervals. The long-acting preparations accumulate during the taper to result in a self-leveling effect of the blood level of the benzodiazepine or barbiturates over time.

Antiepileptic medications, such as carbamazepine or valproic acid, have also been used for the treatment of sedative and benzodiazepine withdrawal. Patients receive rapidly escalating doses of the anticonvulsant to produce therapeutic blood levels over 1 to 2 days. These blood levels are maintained for 7 to 14 days and then tapered. The advantage of using antiepileptic medications is that patients do not receive potentially addictive substances as part of their treatment. This is particularly advantageous for outpatient detoxification, where the patients may be likely to abuse medications.

Following detoxification, the patient should be engaged in long-term treatment. Treatments should be individualized to the patient, but may include residential drug-free programs, outpatient counseling, and self-help groups such as AA or NA.

[edit] Cannabis

Cannabis sativa, also called marijuana or hemp, is a plant indigenous to India but now grown worldwide. The leaves, flowers, and seeds of the plant contain many biologically active compounds, the most important of which is Δ⁹- tetrahydrocannabinol (THC). The biologically active substances are administered by smoking or ingesting dried plant parts (marijuana, bhang, ganja), the resin from the plant (hashish), or extracts of the resin (THC or hash oil). Much of the American population has used marijuana. In 1996, an estimated 10.1 million Americans were regular users of marijuana. The percentage of youth (12 to 17) who have used marijuana appears to be increasing and has doubled from 1992 to 1995 to 7.1% of this population group.

After inhalation or ingestion, THC rapidly enters the CNS. It has biphasic elimination, with a short initial half-life (1 to 2 hours) reflecting redistribution and a second half-life of days to weeks. THC is hydroxylated and excreted in bile and urine. Recent research has demonstrated the presence of cannabinoid receptors on brain cells. The receptor is linked to a G protein and inhibits adenylate cyclase in neurons. THC receptors are widely distributed throughout the brain, and an endogenous neurotransmitter for these receptors is hypothesized.

Cannabis intoxication is characterized by tachycardia, muscle relaxation, euphoria, and a sense of well being. Time sense is altered and emotional lability, particularly inappropriate laughter, may be seen. Performance on psychomotor tasks, including driving, is impaired. Depersonalization, paranoia, and anxiety reactions occur with high doses. Although tolerance to the effects of cannabis occurs with chronic use, cessation of use does not produce significant withdrawal phenomena. Chronic cannabis use has been associated with an amotivational state and a feminization syndrome in men that improves on drug discontinuation. Marijuana has antiemetic and analgesic effects; it stimulates appetite in wasting illness such as AIDS and cancer. It reduces intraocular pressure in glaucoma. Δ⁹-THC is now available by prescription as dronabinol for the medical treatment of these conditions. In Arizona and California, the marijuana leaf is available legally by physician prescription for "medical use," although the U.S. government has challenged its distribution in this manner.

[edit] Treatment.

Treatment of cannabis dependence is similar to treatment of other drug dependencies. As part of the initial assessment, all patients should undergo complete medical and psychiatric evaluations. Short-term goals should focus on reducing or stopping cannabis use. Inpatient treatment may be necessary to achieve an abstinent state. Since many patients with cannabis dependence are adolescents or young adults, family involvement in assessment and treatment is important. Long-term treatment should involve addictive disorder specialists. Often, a change in social situation is necessary to decrease drug availability and reduce peer pressure. Individual and group psychotherapy may be useful for understanding the role of the drug in the individual's life, improving self-esteem, and providing alternate methods of relieving psychosocial distress. Self-help groups can provide group and individual support and are most effective when patients are matched with an appropriate peer group.

[edit] Opioids

Opioid abuse and dependence are significant social and medical problems in the United States, with an estimated opioid addict population of greater than 500,000. These patients are frequent users of medical and surgical services because of the multiple medical sequelae of intravenous drug use, and the crime and violence associated with the addict lifestyle. Psychiatric disorders, particularly anxiety disorders and affective disorders, are also common in opioid-dependent patients. Most opioid users are at least occasional intravenous injectors, which places them at risk for infectious hepatitis, HIV, and other infections. Over the past decade, there has been an increasing trend toward smoking or "snorting" heroin, as users have become aware of the risks of HIV infection associated with intravenous drug use.

Opiate drugs have effects on many organ systems. Their action is due to stimulation of receptors for endogenous hormones, enkephalins, endorphins, and dynorphins. There exist at least three distinct opioid receptors, which are designated by the Greek letters μ, κ, and δ. Drugs that act primarily through μ-receptor effects include heroin, morphine, and methadone; such drugs produce analgesia, euphoria, and respiratory depression. Drugs that are mediated through the κ-receptor include the so-called mixed agonist-antagonists, buprenorphine, butorphanol, and pentazocine, which produce analgesia, but less respiratory depression. The δ-receptor appears to bind endogenous opioid peptides.

[edit] Treatment of Opioid Intoxication.

During opiate intoxication, drugs cause a suppression of central and peripheral nervous system activity. Important diagnostically, pupils are constricted and poorly reactive. Hypotension and constipation are common findings. Effects of severe intoxication include seizures, pulmonary edema, respiratory suppression, and cardiovascular arrest.

Opiate overdose is life-threatening and should be suspected in any patient presenting with coma and respiratory suppression. Treatment of overdose includes support of cardiovascular and respiratory functions. Opiate intoxication can be reversed with the opiate antagonists naloxone (Narcan) or nalmefene. Naloxone is given intravenously in doses of 0.4 to 0.8 mg every 20 minutes as required. The dose is titrated by response until an upper limit of 24 mg is attained over a 12-hour period. Opioid antagonists rapidly reverse coma and respiratory suppression caused by opioids, but do not reverse CNS depression caused by other sedative drugs, including alcohol. Naloxone and nalmefene will precipitate withdrawal in any patient who is dependent on opioids, causing the patient whose life was just saved to be most ungrateful.

[edit] Diagnosis and Treatment of Opioid Withdrawal.

Opiate withdrawal, although rarely life-threatening, is subjectively distressing and is marked by an intense drive to use more opiates. The period of peak withdrawal depends on the opiate used: for short-acting opiates such as morphine, heroin, or meperidine, the peak withdrawal is 1 to 3 days and duration is 5 to 7 days. For longer acting opiates, such as methadone, the peak is 3 to 5 days and the duration 10 to 14 days. When opiate receptors are no longer stimulated by opiates (e.g., morphine or heroin), a rebound excitation of norepinephrine occurs mediated through α₂-receptors and contributes to the signs and symptoms of withdrawal.

Signs of opiate withdrawal are: (1) pulse 10 beats per minute or more over baseline or over 90 if there is no history of tachycardia and the baseline is unknown; systolic blood pressure 10 mm Hg or more above baseline or over 160/90 in patients without hypertension; (2) dilated pupils; (3) gooseflesh, diaphoresis, rhinorrhea, lacrimation, diarrhea; (4) agitation, insomnia, mood lability; and (5) drug seeking. Symptoms of opiate withdrawal are intense muscular cramps, anxiety, arthralgias, nausea, malaise, and compelling desire to use opiates.

Opiate withdrawal can be minimized with an opiate taper or with clonidine. A gradually decreasing dose of any opioid can be used for detoxification. Methadone is most commonly used due to its long half-life and once-daily oral administration. Those patients for whom an opiate taper is indicated include intravenous users, inpatients, users of methadone, and those who have medical and psychiatric complications and poor compliance with withdrawal from opiates. Those patients for whom clonidine is indicated are intranasal users, outpatients, and those who are motivated for a drug-free state.

Methadone detoxifications are performed by substituting the abused opioid with methadone and then gradually decreasing the dose of methadone over a period of up to 21 days, as specified by federal law. Initially, patients should be given 10 to 20 mg methadone orally every 2 to 4 hours until withdrawal symptoms are suppressed. The total daily dose received is typically 20 to 40 mg for heroin addicts. This dose is then decreased by approximately 10% daily. For patients unable to receive oral medications, the same dose of intramuscular methadone may be administered twice daily in divided doses.

The α₂-adrenergic agonist, clonidine hydrochloride, suppresses many autonomic signs and symptoms of opioid withdrawal. Clonidine acts at presynaptic noradrenergic nerve endings in the locus ceruleus of the brain, and blocks the adrenergic discharge produced by opioid withdrawal. Clonidine has been reported as clinically effective for suppressing opioid withdrawal following opioid discontinuation. Its main side effects include orthostatic hypotension, sedation, and dry mouth.

Clonidine detoxification is performed as follows: On the day before beginning clonidine, the usual dose of opioid is received. On day 1, the opioid is stopped completely, and instead, clonidine is given at a dose of 0.1 mg each 8 hours. From day 2 to day 4 the dose of clonidine is gradually increased to suppress withdrawal signs and symptoms, but without allowing blood pressure to decrease below 80 mm systolic and 60 mm diastolic. Typically, a dose of 0.6 to 1.2 mg clonidine is required by day 4, but the dose will depend on the quantity of opioid used. This dose continues until day 7 for patients using short-acting opioids, such as heroin, morphine, or meperidine, and until day 10 to 12 for those using longer acting methadone. The clonidine dose is then reduced by 0.2 to 0.3 mg per day until discontinued. Outpatient clonidine detoxification has been performed without significant morbidity but requires close monitoring with daily blood pressure determinations. Clonidine is less effective in attenuating drug craving, insomnia, and arthralgias and myalgias. Insomnia is best treated with a hypnotic such as chloral hydrate or a benzodiazepine. Muscle and joint pains respond to acetaminophen or ibuprofen.

[edit] Ultrarapid Opioid Detoxification.

Because the opioid withdrawal syndrome is so physically and emotionally distressing, it often leads patients to reinstitute their opioid use. The administration of opioid antagonists, such as naloxone or naltrexone, during the withdrawal period reduces the duration of withdrawal, but significantly increases withdrawal intensity. Recently, a number of physicians have combined opioid antagonists and clonidine with conscious sedation or general anesthesia in a technique called ultrarapid opioid detoxification (UROD). Using this technique, opioid-dependent patients may be detoxified in less than 24 hours. Proponents of the technique claim that the detoxification is safe and results in long-term abstinence. However, there are few controlled studies to compare the efficacy and safety of UROD with more traditional detoxification methods.

[edit] Maintenance Treatment of Opioid Dependence.

The most widely used pharmacologic treatments for opioid-dependent individuals include pharmacologic maintenance (substitution) treatments with the opiate agonists methadone and l-α-acetylmethadol (LAAM); maintenance with the partial opiate agonist buprenorphine; and opiate antagonist therapy with naltrexone. All of these medications are best used in the setting of a structured, maintenance treatment program, which includes monitored medication administration, periodic random urine toxicologic screening, and intensive psychologic, medical, and vocational services. Maintenance treatments reduce use of illicit opiates by increasing drug tolerance, thereby decreasing the subjective effects of administered illicit opiates, and by stabilizing mood, thereby decreasing self-medication. Maintenance treatments also provide an incentive for treatment so that patients can be exposed to other therapies.

[edit] Methadone Maintenance.

Methadone is a synthetic opiate that is orally active, possesses a long-duration of action, produces minimal sedation or "high," and has few side effects at therapeutic doses. Since its introduction in 1965, methadone maintenance has become a major modality of long-term treatment of opioid abuse and dependence. Currently, over 100,000 individuals are maintained on methadone in the United States. Although some programs may have waiting lists for treatment, patients who are pregnant or who have significant problems, such as renal failure, heart disease, or AIDS, are usually accepted directly without a waiting period.

Many studies have shown the efficacy of methadone maintenance in the treatment of addicts who are dependent on heroin and other opiates. Methadone-treated patients show increased treatment retention, improved physical health, decreased criminal activity, increased employment, and decreased chance of becoming HIV-positive. Methadone is most effective in the context of a program that provides intensive psychosocial and medical services and adequate methadone dosing. As mentioned above, the use of methadone for maintenance is highly regulated by government agencies. Maintenance programs must be licensed and follow regulations regarding treatment eligibility, allowable methadone dosages, frequency of urine toxicologic monitoring, and provision of psychosocial and medical services.

Methadone is dissolved in a flavored liquid that is administered to patients daily, under observation. Long-standing program participants are allowed "take-home" doses of methadone, which patients may self-administer. Methadone doses usually range from 20 mg per day to over 100 mg per day. Higher doses are shown to be associated with better treatment retention. Urine toxicologic screening is performed randomly and periodically to assess treatment compliance. Counseling, medical care, and other social services are provided to patients on a regular basis.

If patients receiving methadone maintenance are hospitalized, their usual daily dose of methadone should be continued in the hospital. It is important to maintain frequent communication with the methadone program, particularly regarding changes in methadone dosage and discharge planning. If opioid pain medication is necessary, patients should receive additional short to intermediate acting opioids, such as meperidine or oxycodone, besides their usual dose of methadone, rather than increasing the methadone dose (see below). Certain mixed agonist-antagonist medications, such as pentazocine and butorphanol, should be avoided, since they may precipitate withdrawal.

[edit] l-α-Acetylmethadol Acetate.

LAAM is a long-acting, orally active opiate with pharmacologic properties that are similar to methadone. Studies on LAAM have shown it to be equal or superior to methadone maintenance in reducing IV drug use, when used in the context of a structured treatment program. The advantages of LAAM include a slower onset of effects and a longer duration of action than methadone. This allows LAAM to be administered only three times per week, and eliminates the need for take-home medications that may be diverted to illegal uses. However, some patients dislike the inability to get take-home medication and reject LAAM in favor of methadone. Patients treated with LAAM should be started on 20 mg administered three times weekly, with the dose increased weekly in 10 mg increments as necessary. Doses up to 80 mg three times weekly are safe and effective.

[edit] Buprenorphine.

Buprenorphine is a partial agonist opiate medication (mixed agonist-antagonist), originally used medically as an analgesic. The drug has both agonist and antagonist properties—agonist properties predominate at lower doses and antagonist properties predominate at higher doses. Buprenorphine has two major advantages over methadone: it is less likely to be abused and the withdrawal syndrome is much milder. At the time of publication of this book, buprenorphine has not yet been approved for opioid dependence by regulatory agencies; however, its use is widespread in research settings and approval is expected shortly.

A structured treatment program combining counseling and daily dosing with buprenorphine has been shown to be effective in the maintenance treatment of narcotics addicts. Buprenorphine may also reduce cocaine use. Buprenorphine doses usually range from 4 mg per day to up to 16 mg per day, administered sublingually, since the medication is not effective orally. Advantages of buprenorphine include a milder withdrawal syndrome on discontinuation and less potential for abuse, as agonist effects diminish at higher doses. Opioid-dependent patients may be started on 2 to 4 mg buprenorphine immediately after opiates are discontinued, and the dose of buprenorphine titrated to 8 to 16 mg over several days.

[edit] Opioid Antagonist Therapy.

Opioid antagonist therapy reduces the use of illicit drugs by blocking the effect of the drugs at opioid receptors, leading to decreased use. There is some evidence that opiate antagonists may also block craving. Naltrexone is an orally active opioid antagonist approved for the treatment of opiate dependence and narcotic addiction. Naltrexone blocks the intoxicating effects of opioids and has few effects in individuals not dependent on opioids. The usual dose of naltrexone is 50 mg per day, administered orally, although three times weekly dosing with 100, 100, and 150 mg has also been shown to be effective. High doses of naltrexone have been associated with hepatotoxicity; however, deleterious hepatic effects are rarely observed with 50 mg per daily dosing. Other common side effects include anxiety, sedation, and nausea. Naltrexone therapy has been shown to be most effective in motivated individuals with good social supports (such as health care professionals and federal probationers) and appears less helpful for street heroin addicts. Although any physician may prescribe naltrexone, the medication is most effective when part of a comprehensive rehabilitative program.

[edit] Drug-Free Treatment.

Nonpharmacologic and behavioral treatment modalities are quite efficacious in the treatment of opioid dependence. Such treatments include individual and group counseling, residential treatment, and self-help programs. Long-term residential treatment may be most useful for the chronic opioid abuser who requires a change in lifestyle and vocational and psychologic rehabilitation. Residential programs may differ in lengths of stay, treatment intensity, and theoretic orientation. Attending NA is helpful for many patients. Recently, needle-exchange programs have become common. Although these programs do not provide treatment, per se, they reduce the risks of acquiring infectious hepatitis and HIV by providing clean syringes and needles to addicts in exchange for used injection equipment.

[edit] Pain and Addiction.

A particularly difficult clinical problem is the treatment of pain in patients with addiction. Patients with addictive disorders are prone to conditions that produce pain and require analgesic treatment. Drug and alcohol use are major causes of injuries due to accidents and violence. The medical consequences of drug and alcohol use include painful conditions such as pancreatitis, cancers, infections, and HIV-related illnesses. Important issues in treating patients with combined addictive disorders and pain include the type of drug producing dependence (e.g., alcohol, opiates), whether or not the patient is in addiction treatment, and the type of addiction treatment (drug-free, substitution, or antagonist therapy).

All such patients should be entered into an addiction program that coordinates treatment with the physicians providing the treatment for pain. When analgesic medications are required, nonnarcotic substances should be used, if possible. If narcotic analgesics are required, the type of addiction treatment that the patient is receiving will influence analgesic therapy. Patients receiving drug-free, abstinence-oriented therapy will respond to opioids, but require careful monitoring to reduce the chances of abuse and dependence. Those receiving substitution therapy with methadone, LAAM, or buprenorphine may require higher doses of narcotic analgesics because of their increased tolerance. A different opioid medication, such as meperidine or oxycodone, should be utilized. This differentiates the use of opioids for analgesia from the use of opioids for maintenance and does not change the dose of the agent used for substitution therapy. For patients receiving antagonist therapy with naltrexone, the effect of opioids is blocked during the period of antagonist therapy and for 24 to 72 hours after therapy. Stopping the antagonist 1 to 3 days prior to scheduled surgery or dental procedures will remove the opioid blockade. If opioids are needed emergently, higher doses of opioids can overcome the blockade, since naltrexone is a competitive antagonist. However, the opioid administration must be performed with careful monitoring.

[edit] Cocaine and Other Stimulants

The use of CNS stimulants, such as cocaine and amphetamines, is extremely common. The prevalence of cocaine use peaked in the mid-1980s and has slowly declined since. Based on the 1996 National Survey of Drug Abuse, over 20 million Americans tried cocaine at least once and 2.6 million used it during the preceding year. Cocaine and amphetamines are administered by intranasal "snorting" of powder, smoking, or intravenous injection. Amphetamines may also be used orally. Freebase cocaine base is now widely available as crack, which is potent, inexpensive, and easily distributed. Crack vapor is inhaled through heated pipes or by adding a small piece to a burning cigarette.

Cocaine has major physiologic and behavioral effects: (1) it is a local anesthetic of high potency that blocks the initiation and propagation of nerve impulses by affecting the sodium conductance of cell membranes; (2) it is a potent sympathomimetic agent that potentiates the actions of catecholamines in the autonomic nervous system and a potent vasoconstrictor; and (3) it is a potent stimulant of the CNS, potentiating the action of central catecholamine neurotransmitters, norepinephrine, and dopamine. Amphetamines have similar actions to cocaine, although they are not local anesthetics. Stimulants block the reuptake of dopamine and other catecholamines and increase their effects on postsynaptic receptors. However, after prolonged use, stimulants deplete the presynaptic supplies of these neurotransmitters.

Signs and symptoms of cocaine and amphetamine intoxication are sympathomimetic:dilated and reactive pupils, tachycardia, elevated temperature, elevated blood pressure, dry mouth, perspiration or chills, nausea and vomiting, tremulousness, hyperactive reflexes, repetitious compulsive behavior, stereotypic biting or self-mutilation, cardiac dysrhythmias, and flushed skin. Particularly common and serious psychiatric symptoms during intoxication are depression and suicidal and homicidal ideation. Chronic users have poor self-care, weight loss, and wasting. Cocaine overdose produces hyperpyrexia, hyperreflexia, and seizures, which may progress to coma and respiratory arrest.

The plasma half-life of cocaine following oral nasal or intravenous administration is approximately 1 to 2 hours, which correlates with its behavioral effects. With the decline in plasma levels, most users experience a period of dysphoria or "crash," which often leads to additional cocaine use within a short period. The dysphoria is intensified and prolonged following repeated use.

[edit] Treatment.

The treatment of acute stimulant intoxication is essentially supportive. Patients with mild intoxication should be monitored in a supportive, protected environment that minimizes sensory stimulation. Those with severe anxiety or paranoia may benefit from benzodiazepines and low-dose neuroleptics. Patients with severe intoxication, coma, seizures, and hyperpyrexia require intensive care treatment with respiratory and circulatory system support.

The optimal treatment of the chronic cocaine user is still not established. Cessation of stimulant use is not followed by a physiologic withdrawal syndrome of the magnitude of that seen with opioids or alcohol; however, intense dysphoria, depression, and drug craving often occur and make abstinence difficult. Psychotherapy, group therapy, and behavior modification are useful in maintaining abstinence.

Some psychiatric and drug hospitals offer short-term inpatient cocaine treatment, although managed care generally does not support inpatient treatment of cocaine. For recidivists, long-term residential drug-free programs, including therapeutic communities, may be helpful, providing intensive psychologic treatment and drug education in a drug-free environment. Self-help groups such as NA may be useful both as a primary treatment modality for cocaine dependence and as an adjunct to other treatment. An innovative, behaviorally oriented treatment program using payment vouchers to provide positive reinforcement for cocaine abstinence has shown considerable success in reducing cocaine use in research settings.

There is interest in pharmacologic agents as adjunctive treatments for cocaine dependence. Several reports have shown efficacy of antidepressant agents such as imipramine, desipramine, fluoxetine, or trazodone in reducing cocaine craving and decreasing use. The medication doses used were similar to those used for antidepressant therapy. Although there have been reports that carbamazepine, amantadine, and bromocriptine may partially block cocaine craving, controlled clinical trials have not shown them to be effective. At the present time, no pharmacologic agent has been proven effective as a treatment for cocaine dependence.

Certain psychiatric disorders such as depression and attention deficit disorder may be common in stimulant users. Recognition and treatment of these underlying disorders may be necessary to stop cocaine use. In addition, many stimulant users also use alcohol or other drugs, particularly sedatives and heroin, and may require treatment for these substances as well.

[edit] Caffeine

Caffeine and the related methylxanthines theophylline and theobromine are consumed by more than 80% of the population. These drugs are found in coffee, tea, cola and other carbonated drinks, chocolate, and many prescribed and over-the-counter medications, including stimulants (NoDoze), appetite suppressants (Dexatrim), analgesics (Anacin, APC tablets), and cold and sinus preparations (Dristan, Contac).

Knowledge of the extent of the patient's use of caffeine and other methylxanthines is important in the overall assessment and treatment of the primary care patient. CNS effects of caffeine include psychomotor stimulation, increased attention and concentration, and suppression of the need for sleep. Low to moderate doses of caffeine can produce sleep disturbances and anxiety, and may increase requirements for neuroleptic or sedative medications. At high doses and in sensitive individuals, caffeine and other methylxanthines produce tremor and agitation. Cardiac effects include a mild tachycardia, premature ventricular contractions (PVCs), and a slight increase in systolic blood pressure.

Clinically significant caffeine withdrawal is commonly observed in even low to moderate regular caffeine users following reduced caffeine intake. Lethargy, hypersomnia, irritability, and severe headache characterize the caffeine withdrawal syndrome. The duration of withdrawal is usually 24 to 72 hours. The signs and symptoms of caffeine intoxication or caffeine withdrawal may complicate medical or psychiatric treatment by increasing patient distress and by leading to an unnecessary workup for other disorders.

Methylxanthines produce physiologic effects through actions at the cellular level. They produce cardiac stimulation, diuresis, bronchodilation, and CNS stimulation through several mechanisms. They inhibit the enzyme cyclic adenosine monophosphate (AMP) phosphodiesterase and increase intracellular levels of this cyclic AMP, thereby augmenting the action of many hormones and neurotransmitters. Methylxanthines also have a direct inhibitory effect on adenosine receptors.

Treatment of caffeine dependence limits consumption of caffeine-containing foods, medications, and beverages. Beverages such as coffee or cola may be substituted with decaffeinated forms. Often, patients are unaware of the extent of their caffeine consumption. They require education about the caffeine content of their diet and medications. Withdrawal symptoms such as headache and lethargy are best treated with slow caffeine taper and with analgesics and rest.

[edit] Hallucinogens and Phencyclidine (PCP)

Many drugs are used for their psychotomimetic or hallucinogenic effects. These include the psychedelics lysergic acid diethylamide (LSD), mescaline, psilocybin, and dimethyltryptamine; hallucinogenic amphetamines such as methylenedioxyamphetamine (MDA) and methylenedioxymethamphetamine (MDMA, or ecstasy); PCP, ketamine and similarly acting arylcyclohexylamines; and anticholinergics, such as scopolamine. All cause a state of intoxication characterized by hallucinosis, affective changes, and delusions. The mechanism of action of hallucinogens is not well understood and varies according to the drug. LSD and amphetamines are thought to act on dopaminergic and/or serotonergic brain systems, especially the 5HT-2 receptor. PCP and ketamine act at sigma sites on glutamate receptors. Anticholinergics act at muscarinic cholinergic receptors.

[edit] Diagnosis and Treatment of Hallucinogen Intoxication.

Cognitive or memory impairment, disorientation, and confusion often occur in intoxication from psychedelic use. Psychedelic agents also produce electroencephalogram (EEG) changes similar to those seen during rapid eye movement (REM) sleep, which may account for the dreamlike quality of the high reported by those using this class of drugs. Most cases of hallucinogen intoxication are short-lived (lasting several hours) and resolve without incident; however, occasionally, prolonged drug-induced psychoses may occur. Also, some users may report persistent visual trails and flashbacks of the hallucinogen experience. Hallucinogens may precipitate mania or psychosis in individuals with a previous personal history or a family history of these psychiatric disorders.

PCP and the related drug ketamine are particularly dangerous drugs. Those under the influence show impaired judgment and impulsiveness that place users and others at risk for harm. Symptoms of PCP intoxication are hyperactivity, insensitivity to pain, hallucinations, paranoid delusions, and memory loss. Signs include hypertension, tachycardia, eyelid retraction (producing a wide-eyed stare), dry flushed skin, dilated pupils, nystagmus, and an excitable, angry affect. The analgesic and anesthetic action of PCP reduces pain perception and imparts the user with the capability of great motor strength not limited by pain (e.g., breaking out of restraints and overpowering staff). Ketamine, used clinically as a dissociative anesthetic in pediatric surgery, has become increasingly popular as a party drug ("Special K").

The differential diagnosis of hallucinogen-or PCP-induced psychosis includes schizophrenia, bipolar affective disorder, delusional disorder, and organic mental disorders such as encephalitis, brain tumors, and toxic encephalopathies.

[edit] Treatment of Hallucinogen Intoxication.

Treatment includes supportive measures in a quiet setting to prevent patients from harming themselves or others, to maintain cardiovascular and respiratory functions, and to ameliorate agitation and psychotic symptoms until the effects of the drug subside. Pharmacologic treatment for the management of behavioral symptoms is sometimes required. Lorazepam (Ativan) 1 to 2 mg po or IV q 1 to 2 hours prn or diazepam (Valium) 5 to 10 mg po q 2 to 4 hours prn can be given to calm and sedate. For PCP, symptoms of intoxication are diminished or reversed by haloperidol 5 to 10 mg intramuscularly or orally every 1 to 6 hours as needed for behavioral control. Lorazepam 1 to 2 mg IV or diazepam 5 to 10 mg po q 1 to 6 hours can also be given. Following detoxification, the patient should be engaged in long-term treatment, which may include residential programs, outpatient counseling, and self-help groups such as NA.

[edit] Inhalants

Inhalants are volatile organic compounds that are inhaled for their psychotropic effects. Substances in this class include organic solvents (gasoline, toluene, ethyl ether, fluorocarbons) and volatile nitrates (nitrous oxide, amyl and butyl nitrate). Inhalants are readily available in households, stores, and worksites. At low doses, inhalants induce mood changes (especially euphoria), hallucinosis, and ataxia; at high doses they induce dissociative states and sedation. A main danger of inhalants is suffocation, since inhalant substances can displace oxygen and can reduce respiratory drive. Consequences of organic solvent use include bone marrow suppression, hepatotoxicity, and both central and peripheral neuropathies. Cardiac dysrhythmias may occur, leading to sudden death. Inhaled nitrates may produce hypotension and methemoglobinemia. The typical user of inhalants is a male adolescent. According to the National Household Survey on Drug Abuse, 9.1% of 12 to 17 year olds and 12.8% of 18 to 25 year olds have tried an inhalant at least once.

The optimal treatment of the inhalant user is similar to that for any substance dependence. Patients need comprehensive medical and psychiatric assessments, as well as addiction treatment. Since inhalant users are usually adolescents, treatment should involve the family. Long-term residential treatment may be helpful in the treatment of heavy users.

[edit] Anabolic Steroids

The use of anabolic steroids, once predominantly a problem in fanatic athletes, has now become a relatively common problem in adolescents. A recent study found 6.5% of adolescent boys and 1.9% of adolescent girls reported using anabolic steroids without a physician's prescription. The use of anabolic steroids is associated with the use of other substances, including cocaine, alcohol, injectable drugs, marijuana, and cigarettes.

Medical complications of anabolic steroid use include myocardial infarction, stroke, and hepatic disease. Users are usually completely naïve or deny the medical hazards of anabolic steroid use. HIV infection has been associated with shared needle use in steroid injectors. Psychiatric symptoms associated with anabolic steroid use include severe depression, psychotic (paranoid) symptoms, aggressive behavior, homicidal impulses, euphoria, irritability, anxiety, and hyperactivity. Although these symptoms gradually abate with drug discontinuation, depression, fatigue, decreased sex drive, insomnia, anorexia, and body image dissatisfaction may continue.

The treatment of anabolic steroid dependence should be within the same general model of other addictions, with due consideration to the high likelihood of dependency on other drugs, particularly in adolescents. Psychiatric management of drug-induced mood and paranoid syndromes is necessary. Issues regarding narcissistic body image are often present in certain athletes and body builders and should be considered in the psychotherapy of such individuals.

[edit] ADDITIONAL READINGS

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